The role of hepatic microsomal mixed function oxidase metabolism of fluorinated ether anesthetics in potentiating the toxicity of the anesthetics will be investigated in rats. In vivo and in vitro studies will be performed. In vitro studies with highly purified, reconstituted systems of cytochromes P-450 and NADPH cytochrome P-450 reductase or with microsomal suspensions will be used to determine the metabolic pathways of anesthetic metabolism and the role of these pathways in the related anesthetic toxicity. The potential for the metabolic formation of reactive epoxide intermediates and the toxicity of such intermediates will be investigated. The effect of epoxide hydratase and epoxide hydratase inhibitors in enhancing and diminishing the toxicity of the anesthetics will be related to the formation of epoxide intermediates. The mechanism whereby metabolism of anesthetics produces destruction of cytochrome P-450 will be examined. The results of these studies should provide an understanding of why anesthetics become toxic and to what extent the anesthetic related destruction of cytochrome P-450 will affect co-administered drugs.